Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists.

Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource environments. The present study tests this hypothesis across diverse timeframes, branches of immunity, and conditions of energy availability among humans. Using a prospective mixed-longitudinal design, we collected anthropometric and blood immune biomarker data from 261 Amazonian forager-horticulturalist Shuar children (age 4-11 y old). This strategy provided baseline measures of participant stature, s.c. body fat, and humoral and cell-mediated immune activity as well as subsample longitudinal measures of linear growth (1 wk, 3 mo, 20 mo) and acute inflammation. Multilevel analyses demonstrate consistent negative effects of immune function on growth, with children experiencing up to 49% growth reduction during periods of mildly elevated immune activity. The direct energetic nature of these relationships is indicated by (i) the manifestation of biomarker-specific negative immune effects only when examining growth over timeframes capturing active competition for energetic resources, (ii) the exaggerated impact of particularly costly inflammation on growth, and (iii) the ability of children with greater levels of body fat (i.e., energy reserves) to completely avoid the growth-inhibiting effects of acute inflammation. These findings provide evidence for immunologically and temporally diverse body fat-dependent tradeoffs between immune function and growth during childhood. We discuss the implications of this work for understanding human developmental energetics and the biological mechanisms regulating variation in human ontogeny, life history, and health.

Variability of C-reactive protein in first-generation Ecuadorian immigrants living in the United States.

OBJECTIVES: Establish the variability of C-reactive protein (CRP) within a population of first-generation immigrants living in the United States. Prior work has theorized that individuals with high levels of childhood pathogen exposure may have lower CRP levels in adulthood, and therefore that for these individuals, CRP may not be as accurate an index of chronic disease risk related to low-level inflammation as is presumed based on data from wealthy populations. This potentially has major implications for the interpretation of CRP as a biomarker of chronic inflammation. METHODS: This longitudinal study collected a total of 125 dried blood spot (DBS) samples from 31 participants (median 4 samples each) and CRP levels in these DBS were assayed by enzyme-linked immunosorbant assay. Surveys were administered to characterize childhood pathogen exposure, and current illness. Variance was estimated using mixed effects regression models. RESULTS: On average, participants were adults (mean = 41.9 years old) who had immigrated to the United States nearly 20 years prior to the study and had nearly universally experienced childhood helminth infection and other major pathogen exposures. Median serum-equivalent CRP was 0.77 mg/L. Individuals reliably differed in subacute CRP levels, and, depending on whether untransformed or log-transformed CRP was the outcome variable, 45% or 62% of variance in CRP was attributable to between-individual differences. CONCLUSIONS: The variability of CRP levels in individuals with relatively high childhood pathogen exposure is comparable to previously reported studies in North America and Europe. However, CRP values are relatively low. CRP is an appropriate measure of subacute inflammation in this sample.

Endocrinology, energetics, and human life history: A synthetic model.

Human life histories are shaped by the allocation of metabolic energy to competing physiological domains. A model framework of the pathways of energy allocation is described and hormonal regulators of allocation along the pathways of the framework are discussed in the light of evidence from field studies of the endocrinology of human energetics. The framework is then used to generate simple models of two important life history transitions in humans, puberty and the postpartum return to full fecundity in females. The results of the models correspond very closely to observations made in the field.

Lack of support for relation between woman's masculinity preference, estradiol level and mating context.

It has been proposed that women's preferences for male facial sexual dimorphism are positively correlated with conception probability and differ between short- and long-term mating contexts. In this study, we tested this assumption by analyzing relationships between estradiol levels to the women's preferences of male faces that were manipulated to vary in masculinity. Estradiol was measured in daily saliva samples throughout the entire menstrual cycle collected by Polish women with regular menstrual cycles. In our analyses, we included the three most commonly used definitions of the fertile window in the literature. After computing the overall masculinity preference of each participant and measuring hormone levels, we found that i) the timing of ovulation varied greatly among women (between -11 and -17days from the onset of the next menses, counting backwards), ii) there was no relationship between daily, measured during the day of the test (N=83) or average for the cycle (N=115) estradiol levels and masculinity preferences, iii) there were no differences in masculinity preferences between women in low- and high-conception probability phases of the cycle, and iv) there were no differences in masculinity preferences between short- and long-term mating contexts. Our results do not support the idea that women's preferences for a potential sexual partner's facial masculinity fluctuate throughout the cycle.

Alcohol consumption, endogenous estrogen and mammographic density among premenopausal women.

INTRODUCTION: Alcohol consumption may promote aromatization of androgens to estrogens, which may partly explain the observations linking alcohol consumption to higher breast cancer risk. Whether alcohol consumption is associated with endogenous estrogen levels, and mammographic density phenotypes in premenopausal women remains unclear. METHODS: Alcohol consumption was collected by self-report and interview, using semi quantitative food frequency questionnaires, and a food diary during seven days of a menstrual cycle among 202 premenopausal women, participating in the Energy Balance and Breast Cancer Aspects (EBBA) study I. Estrogen was assessed in serum and daily in saliva across an entire menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms taken between days 7-12 of the menstrual cycle. Multivariable regression models were used to investigate the associations between alcohol consumption, endogenous estrogen and mammographic density phenotypes. RESULTS: Current alcohol consumption was positively associated with endogenous estrogen, and absolute mammographic density. We observed 18 % higher mean salivary 17ß-estradiol levels throughout the menstrual cycle, among women who consumed more than 10 g of alcohol per day compared to women who consumed less than 10 g of alcohol per day (p = 0.034). Long-term and past-year alcohol consumption was positively associated with mammographic density. We observed a positive association between alcohol consumption (past year) and absolute mammographic density; high alcohol consumers (≥7 drinks/week) had a mean absolute mammographic density of 46.17 cm(2) (95 % confidence interval (CI) 39.39, 52.95), while low alcohol consumers (<1 drink/week) had a mean absolute mammographic density of 31.26 cm(2) (95 % CI 25.89, 36.64) (p-trend 0.001). After adjustments, high consumers of alcohol (≥7 drinks/week), had 5.08 (95 % CI 1.82, 14.20) times higher odds of having absolute mammographic density above median (>32.4 cm(2)), compared to low (<1 drink/week) alcohol consumers. CONCLUSION: Alcohol consumption was positively associated with daily endogenous estrogen levels and mammographic density in premenopausal women. These associations could point to an important area of breast cancer prevention.

Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

Diurnal variation in salivary cortisol across age classes in Ache Amerindian males of Paraguay.

OBJECTIVES: Cortisol levels exhibit a diurnal rhythm in healthy men, with peaks in the morning and troughs in the evening. Throughout age, however, this rhythm tends to flatten. This diurnal flattening has been demonstrated in a majority of industrialized populations, although the results have not been unanimous. Regardless, little attention has been paid to nonindustrialized, foraging populations such as the Ache Amerindians of Paraguay. As testosterone levels had previously been shown to diminish with age in this population (Bribiescas and Hill [2010]: Am J Hum Biol 22: 216-220), we hypothesized that cortisol levels would behave similarly, flattening in rhythmicity over age. METHODS: We examined morning and evening salivary cortisol samples in Ache Amerindian men in association with age (n = 40, age range 20-64 years). RESULTS: Men in the first age class (<20-29 years) exhibited significantly different morning (AM) and evening (PM) values as did men in the second age class (30-39 years). However, men in the third and fourth age classes (40-49 years, and >50 years, respectively) did not exhibit a significant difference between AM and PM values. CONCLUSION: Ache Amerindian men exhibit a flattening of the diurnal rhythm across age classes. Our results were able to capture both within- and between-individual variations in cortisol levels, and reflected age-related contrasts in daily cortisol fluctuations. The flattening of the diurnal rhythm with age among the Ache may reflect a common and shared aspect of male senescence across ecological contexts and lifestyles. Am. J. Hum. Biol. 27:344-348, 2015. © 2014 Wiley Periodicals, Inc.

Digit ratio (2D:4D) does not correlate with daily 17ß-estradiol and progesterone concentrations in healthy women of reproductive age.

OBJECTIVES: Second-to-fourth digit ratio (2D:4D) is proposed as a proxy for the prenatal balance of sex hormones, is related to hormone-dependent characteristics in adult life, and is a possible predictor of disease later in life. Here, we studied the relationship between 2D:4D and ovarian steroid hormones (17ß-estradiol and progesterone) among women of reproductive age. METHODS: From 186 healthy premenopausal women, aged 24-37 years, we collected saliva samples daily during the entire menstrual cycle. Data on reproductive and lifestyle characteristics were collected via questionnaires, and anthropometric measurements were performed. RESULTS: No statistically significant relationships were detected between adult women's sex hormone concentrations (17ß-estradiol and progesterone) during the menstrual cycle and 2D:4D, in either left or right hand, when controlling for size at birth, body mass index, and physical activity. CONCLUSIONS: This study shows, for the first time in a large sample of women of reproductive age, that 2D:4D is not a predictor of adult women's sex hormone concentration. The lack of relationship may be because 2D:4D might be genetically determined and is not related to maternal nutritional environment during fetal development. These results support the hypothesis that, in contrast to the nutritional quality of the fetal environment, the fetal hormonal environment (reflected by 2D:4D) does not determine reproductive physiology in later life.

Women who are married or living as married have higher salivary estradiol and progesterone than unmarried women.

OBJECTIVES: Extensive research has demonstrated that marriage and parenting are associated with lower testosterone levels in men, however, very little is known about associations with hormone concentrations in women. Two studies have found lower testosterone in relation to pair-bonding and motherhood in women, with several others suggesting that estradiol levels are lower among parous women than nulliparous women. Here, we examine estradiol and progesterone concentrations in relation to marriage and motherhood in naturally cycling, reproductive age women. METHODS: In 185 Norwegian women, estradiol and progesterone concentrations were assayed from waking saliva samples collected daily over the course of a menstrual cycle. Cycles were aligned on day 0, the day of ovulation. Mean periovulatory estradiol (days -7 to +6) and luteal progesterone (day +2 to +10) indices were calculated. Marital status and motherhood (including age of youngest child) were reported in baseline questionnaires. Multivariable linear regression models were used to examine associations between ovarian hormones, marital status, and motherhood. RESULTS: Women who were married or living as married had higher estradiol than unmarried women (ß = 0.19; 95% CI: 0.02, 0.36) and higher luteal progesterone as well (ß = 0.19; 95% CI: -0.01, 0.39). There were no notable differences in hormone levels in relationship to motherhood status. CONCLUSIONS: Our results indicate that ovarian steroid hormones may be higher among women who are married or living as married, and suggest several possible explanations, however, additional research is needed to elucidate any causal relationships.

Metabolic hypothesis for human altriciality.

The classic anthropological hypothesis known as the "obstetrical dilemma" is a well-known explanation for human altriciality, a condition that has significant implications for human social and behavioral evolution. The hypothesis holds that antagonistic selection for a large neonatal brain and a narrow, bipedal-adapted birth canal poses a problem for childbirth; the hominin "solution" is to truncate gestation, resulting in an altricial neonate. This explanation for human altriciality based on pelvic constraints persists despite data linking human life history to that of other species. Here, we present evidence that challenges the importance of pelvic morphology and mechanics in the evolution of human gestation and altriciality. Instead, our analyses suggest that limits to maternal metabolism are the primary constraints on human gestation length and fetal growth. Although pelvic remodeling and encephalization during hominin evolution contributed to the present parturitional difficulty, there is little evidence that pelvic constraints have altered the timing of birth.

Gene variations in oestrogen pathways, CYP19A1, daily 17ß-estradiol and mammographic density phenotypes in premenopausal women.

INTRODUCTION: High mammographic density is an established breast cancer risk factor, and circulating oestrogen influences oestrogen-regulating gene expression in breast cancer development. However, less is known about the interrelationships of common variants in the CYP19A1 gene, daily levels of oestrogens, mammographic density phenotypes and body mass index (BMI) in premenopausal women. METHODS: Based on plausible biological mechanisms related to the oestrogen pathway, we investigated the association of single nucleotide polymorphisms (SNPs) in CYP19A1, 17ß-estradiol and mammographic density in 202 premenopausal women. DNA was genotyped using the Illumina Golden Gate platform. Daily salivary 17ß-estradiol concentrations were measured throughout an entire menstrual cycle. Mammographic density phenotypes were assessed using a computer-assisted method (Madena). We determined associations using multivariable linear and logistic regression models. RESULTS: The minor alleles of rs749292 were positively (P = 0.026), and the minor alleles of rs7172156 were inversely (P = 0.002) associated with daily 17ß-estradiol. We observed an 87% lower level of daily 17ß-estradiol throughout a menstrual cycle in heavier women (BMI >23.6 kg/m(2)) of rs7172156 with minor genotype aa compared with major genotype AA. Furthermore, the rs749292 minor alleles were inversely associated with absolute mammographic density (P = 0.032). Lean women with rs749292 minor alleles had 70 to 80% lower risk for high absolute mammographic density (>32.4 cm(2)); Aa: odds ratio (OR) = 0.23 (95% CI 0.07 to 0.75). Lean women with rs7172156 minor homozygous genotype had OR 5.45 for high absolute mammographic density (aa: OR = 5.45 (95% CI 1.13 to 26.3)). CONCLUSION: Our findings suggest that two SNPs in CYP19A1, rs749292 and rs7172156, are associated with both daily oestrogen levels and mammographic density phenotypes. BMI may modify these associations, but larger studies are needed.

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women.

BACKGROUND: Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. MATERIALS AND METHODS: Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models. RESULTS: Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17ß-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17ß-estradiol were 1.81 [95% confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17ß-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28). CONCLUSION: Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.

Ovarian function in Samoan women shows stronger association with signals of energy metabolism than fat reserves.

OBJECTIVES: The relative influence of prominent energetic hormones such as insulin and leptin on ovarian steroid production has yet to be determined and demonstrated consistently in vivo. This study reports preliminary findings on the relationship between insulin, leptin, and estradiol, a major ovarian steroid, in a sample of Samoan women. METHODS: Participants were 34 regularly cycling, nonlactating, premenopausal women in the follicular phase of their menstrual cycle with indicators of normal glucose tolerance. Fasting serum samples provided one-time, cross-sectional measures of glucose, insulin, leptin, and estradiol. Main statistical analyses consisted of Student's t-tests, used to determine significant differences in mean estradiol level between contrasting groups of insulin and leptin. RESULTS: Relatively high insulin levels within the normal range of variation showed a positive association with estradiol levels whereas relatively high leptin levels did not. The association between insulin and estradiol appeared to conform to a step-like categorical relationship--with the highest insulin levels exerting the greatest positive effect--rather than a dose-response linear relationship. CONCLUSIONS: This study adds to the growing evidence that peripheral regulation of ovarian function likely involves permissive signals that emphasize a state of energy surplus, related primarily to energy metabolism rather than energy reserves, and warrant more extensive study.

Endocrine responses, weight change, and energy sparing mechanisms during Ramadan among Gambian adolescent women.

OBJECTIVES: Ramadan fasting imposes a diurnal rather than a chronic energetic challenge. When Ramadan occurs during the agricultural season in subsistence populations, diurnal and chronic effects combine. The impact of layered energetic challenges on adolescent activity, metabolism, and body composition have not been quantified. This study compares the effects of a Ramadan (30 July-3 October 2009) and subsequent non-Ramadan (14 July-12 August 2010) agricultural season in 67 Gambian subsistence agriculturalist women between 14 and 20 years old. METHODS: Researchers collected body composition, anthropometric, metabolic, and activity data. Metabolic hormones were measured in weekly urine (C-peptide of insulin) and serum (leptin). Energy expenditure was estimated from heart rate calibrated for oxygen consumption. RESULTS: Participants lost more weight (Wald Chi-square 8.7, P < 0.01) and lean mass (Wald Chi-square 4.7, P < 0.05) in Ramadan than in the non-Ramadan agricultural season. Energy expenditure was lower (Wald Chi-square 11.2, P = 0.001) and there was a negative correlation between resting metabolic rate and energy expenditure in activity (R(2) = 0.097, F = 5.366, P = 0.025) during Ramadan. Leptin and C-peptide were higher during Ramadan (Wald Chi-square 53.7, P < 0.001 and Wald Chi-square 15.0, P < 0.001). CONCLUSIONS: Even using energy sparing behaviors, adolescent women enter negative energy balance when Ramadan and the agricultural season co-occur. Metabolic physiology shows a transient response to high glycemic index foods consumed at night. Older and larger individuals sustain greater losses during Ramadan.

Marriage and motherhood are associated with lower testosterone concentrations in women.

Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes.

Differential changes in steroid hormones before competition in bonobos and chimpanzees.

A large body of research has demonstrated that variation in competitive behavior across species and individuals is linked to variation in physiology. In particular, rapid changes in testosterone and cortisol during competition differ according to an individual's or species' psychological and behavioral responses to competition. This suggests that among pairs of species in which there are behavioral differences in competition, there should also be differences in the endocrine shifts surrounding competition. We tested this hypothesis by presenting humans' closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), with a dyadic food competition and measuring their salivary testosterone and cortisol levels. Given that chimpanzees and bonobos differ markedly in their food-sharing behavior, we predicted that they would differ in their rapid endocrine shifts. We found that in both species, males showed an anticipatory decrease (relative to baseline) in steroids when placed with a partner in a situation in which the two individuals shared food, and an anticipatory increase when placed with a partner in a situation in which the dominant individual obtained more food. The species differed, however, in terms of which hormone was affected; in bonobo males the shifts occurred in cortisol, whereas in chimpanzee males the shifts occurred in testosterone. Thus, in anticipation of an identical competition, bonobo and chimpanzee males showed differential endocrine shifts, perhaps due to differences in perception of the situation, that is, viewing the event either as a stressor or a dominance contest. In turn, common selection pressures in human evolution may have acted on the psychology and the endocrinology of our competitive behavior.

Evolution in health and medicine Sackler colloquium: Making evolutionary biology a basic science for medicine.

New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to use them fully. This article summarizes suggestions from several groups that have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and when and how they should learn it. Our general conclusion is that evolutionary biology is a crucial basic science for medicine. In addition to looking at established evolutionary methods and topics, such as population genetics and pathogen evolution, we highlight questions about why natural selection leaves bodies vulnerable to disease. Knowledge about evolution provides physicians with an integrative framework that links otherwise disparate bits of knowledge. It replaces the prevalent view of bodies as machines with a biological view of bodies shaped by evolutionary processes. Like other basic sciences, evolutionary biology needs to be taught both before and during medical school. Most introductory biology courses are insufficient to establish competency in evolutionary biology. Premedical students need evolution courses, possibly ones that emphasize medically relevant aspects. In medical school, evolutionary biology should be taught as one of the basic medical sciences. This will require a course that reviews basic principles and specific medical applications, followed by an integrated presentation of evolutionary aspects that apply to each disease and organ system. Evolutionary biology is not just another topic vying for inclusion in the curriculum; it is an essential foundation for a biological understanding of health and disease.

Puberty as a life history transition.

BACKGROUND: James Tanner's landmark publication, Growth at Adolescence, was not only the first and most comprehensive treatise on the subject of human pubertal development of its time, its core insights have held up remarkably well over time. REVIEW: This review connects Tanner's contributions to contemporary understanding of puberty as a process fundamentally driven by neuroendocrine maturation. It introduces the concepts of the 'hour-glass of puberty' and 'somatic strategy' as heuristic constructs. The 'hour-glass of puberty' describes the converging pathways of information flow influencing the timing of the neuroendocrine events of puberty and its ramifying consequences throughout the body. Somatic strategy refers to the pattern of sex-specific, adult body morphology that develops at puberty as the individual undergoes a life history transition from juvenile to adult.